A mass spectrometer and a differential ion mobility spectrometer are apparatuses that analyze a measurement target substance by ionization. In the case of the mass spectrometer, the measurement target substance ion is introduced into a vacuum and then separated in accordance with a mass-to-charge ratio m/z to thereby be detected. An additive used by the mass spectrometer includes a derivatization reagent. The derivatization reagent has an effect to raise ionization efficiency of the measurement target substance by bonding a functional group which can be easily ionized to the measurement target substance. In the case of the differential ion mobility spectrometer, ions are caused to collide with a gas and then the ions are separated in accordance with collision cross sections. The differential ion mobility spectrometer uses an organic solvent such as acetone and acetonitrile as the additive. The organic solvent is vaporized to form a cluster with the measurement target substance ion, by which the collision cross section of the ion is changed. As a result, the difference between the collision cross section of a contaminant ion and that of the measurement target substance ion increases to thereby improve the separability.
The sample to be ionized may take a gas state, a liquid state, or a solid state. To ionize a liquid sample, there is adopted a method in which the liquid is atomized and sprayed by using a spray. In an electro spray ionization method, the liquid sample is caused to flow through a thin tube, and then a high voltage is applied to an outlet of the thin tube. The liquid sample is electrically charged by the high voltage applied to the thin tube, which makes the liquid sample existing near the outlet of the thin tube to be atomized in a mist form by the electrical repulsion. In the electro spray ionization method, a nebulizer gas is caused to flow coaxially with the liquid sample. The liquid sample can be stably sprayed by existence of the nebulizer gas. Solvents in the sprayed charged droplets are vaporized to ionize the measurement target substance contained in the droplets. To ionize the liquid sample, also an atmospheric chemical ionization method may be used. In the atmospheric chemical ionization method, the liquid sample is sprayed, and then the molecules in the air are ionized by electric discharge. After that, the electric charge is moved to the measurement target substance by the ion-molecule reaction, and thus the measurement target substance is ionized.
A mixing method of the additive and a liquid atomization technique used in the mass spectrometer are described below as techniques relating to the present invention.
Patent Document 1 discloses a method in which a substance that alters the characteristics of the measurement target substance ion is mixed into a curtain gas flowing into an inlet of an analyzer constituted by a mass spectrometer and a differential type mobility spectrometer. For altering the characteristics of the measurement target substance ion, there are listed substances as follows: a modifier for altering the collision cross section of the measurement target substance ion; a mass calibration agent as a reference for the mass-to-charge ratio m/z needed for the mass axis calibration; and an exchange reagent for replacing part of the measurement target substance with an isotope. While passing through the curtain gas including the modifier, the mass calibration agent, or the exchange agent, the measurement target substance ion reacts with the agents to be altered in the characteristics thereof.
Patent Document 2 describes a structure in which reagent ions used for a proton transfer reaction (PTR) and an electron transfer dissociation (ETD) are introduced into the mass spectrometer. In the structure depicted, the reagent ions and the carrier gas for the reagent ions are supplied from an ion introduction port of the differential ion mobility spectrometer.
Patent Document 3 describes a method using a liquid chromatography mass analyzer in which the measurement target substance is separated from the contaminants by the liquid chromatography (LC), and then the additive is added to the measurement target substance. In a case where an eluate of a strong anion is used as a separation solvent for the LC, the sensitivity for the measurement target substance may be degraded due to ionization suppression by the eluate. To cope with this, the additive is mixed after LC separation to alter the characteristics of the solvent, thereby ionization suppression with the measurement target substance is prevented and the sensitivity is enhanced.
Patent Document 4 describes a method in which in the electro spray ionization method, a gas is caused to flow through a center of the flow passage of the liquid sample to make finer the particle diameter of the sprayed droplets, thereby efficiently vaporizing the solvent.
Patent Document 5 describes a structure in which the droplets of the sample liquid sprayed by using a spray is mixed with charged droplets generated by the electro spray ionization method, thereby performing simultaneously the operation of liquid-liquid extraction and ionization. The charged droplets serve for extracting the measurement target substance from the sample liquid droplets containing the measurement target substance and contaminants, and also for charging and ionizing the measurement target substance thus extracted. In this method, samples including a lot of contaminants can be analyzed by sequentially performing the liquid-liquid extraction.
Patent Document 6 describes a structure in which a flow passage of the additive is connected to the flow passage of the spray gas used for spraying the liquid sample, thereby mixing the additive. In this method, the flow passages of the liquid sample and the additive are separated, so that the LC in which the liquid sample flows is not contaminated. Further, the additive is prevented from directly reacting with substances in the liquid sample and thus forming salts, the apparatus is less contaminated with salts.